W0 2011/000721 A1 I||||||||||||||||||||||||||||||||||||||||||||||||||||||||| - Questel

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To a solution of the silylmannopyranoside previously obtained (3.10 g, 6.33 mmol, 1 eq) in dry THF (63 ml_) at 0 0 C under nitrogen atmosphere 1.81 mL of acetic acid were added slowly (31 .65 mmol, 5 eq). The solution was then warmed at room temperature and 7.60 mL (7.60 mmol, 1.2 eq) of TBAF 1M in dry THF were added. The reaction was stirred overnight at room temperature. After completion (TLC 2:1 ETP:EtOAc) the solution was diluted with brine and then extracted with EtOAc. The organic phases were collected, dried over Na 2 SO 4 , and the solvent was evaporated at reduced pressure. The crude was purified by flash chromatography (4:6 Hex:EtOAc) obtaining 1.71 g of pure product 3 (72%). [ a ] =+42.32 (c: 1.17, CHCI 3 ). 1 H-NMR (400 MHz, CDCI 3 ) δ (ppm): 5.42 (dd, 1H, H 3 , J 3 2 = 3.6 Hz J 3-4 = 10.0 Hz), 5.29 (dd, 1H, H 2 , J 2- i=1 .6 Hz), 5.25 (t, 1H, H 4 , J 4-5 = 10.4 Hz), 4.88 (d, 1H, H 1 ), 3.87 (ddd, 1H, H 78 , J gem = 10.8 Hz J 7B - 8 B= 7.2 Hz, 3.6 Hz), 3.85-3.79 (m, 1H, H 5 ), 3.72 (d, 1H, H 6B , 2.8 Hz), 3.69-3.60 (m, 2H, H 6A , H 7A ) , 3.49 (ddd, 1H, H 8 , 13.6 Hz, 3.6 Hz), 3.42 (ddd, 1H, H 8A , J S A - 7 A= 6.0 Hz), 2.14 (s, 3H, CH 3 CO), 2.08 (s, 3H, CH 3 CO), 2.00 (s, 3H, CH 3 CO). 13 C-NMR (100 MHz, CDCI 3 ) δ (ppm): 171 .0 (COCH 3 ), 170.2 (COCH 3 ), 169.9 (COCH 3 ), 98.0 (C1), 7 1 .1 (C5), 69.6 (C2), 68.8 (C3), 67.1 (C7), 66.5 (C4), 61.4 (C6), 50.5 (C8), 21.0 (CH 3 CO), 20.9 (CH 3 CO), 20.8 (CH 3 CO). HRMS (ESI): Calculated for [Ci 4 H 2 1 N 3 O 9 Na] + = 398.1 1700 Experimental = 398.1 1622.
2 ) synthesis of the pseudo- α( 1 6)-dimannoside 7 acetylated T o a solution of the epoxide 6 (100 mg, 0.467 mmol, 1eq.) and the mannose derivative 3 (525 mg, 1.400 mmol, 3 eq.) in CH 2 C I 2 ( 1 ml) the catalyst Cu(OTf) 2 was added (17 mg, 0.047 mmol, 0.1 eq.). The solution was stirred at room temperature under nitrogen atmosphere overnight. The reaction was followed by TLC (92:8 C H 2 CI 2 : acetone). After completion the solution was diluted with a [ 1 :1] mixture of NH 4 C l sat and NH 4 O H and then extracted with EtOAc. The organic phase was washed with NH 4 Cl sa t till the disappearance of the light blue colour of the aqueous phase, then dried over Na 2 SO 4 . The solvent was evaporated at reduced pressure, giving a crude that was purified by flash chromatography (95:5 CHCI 3 :acetone). 147mg of pure 7 were obtained (yield 53%). [a] =+40.0 (c: 1.00, CHCI 3 ). 1H-NMR (400 MHz, CDCI 3 ) δ (ppm): 5.38-5.29 (m, 2H, H 3M , H 4M ), 5.26 (dd, 1H , H 2M> J 2 -3 = 2 Hz, J 2 1 = 1.6 Hz), 4.85 (d, 1H , H 1M ), 3.99-3.92 (m, 1H, H 5M ), 3.89 (ddd, 1H, H 7 , Jgem =10.8 Hz, J 7A - 8 = 6.8 Hz, J 7A -8' = 3.6 Hz ), 3.85-3.79 (m, 1H, D 2 ), 3.73 (dd, 1H, H 6 , J ge m= 11-2 Hz, J 6B - 5 = 5.2 Hz), 3.69 (s, 3H, OCH 3 ), 3.69 (s, 3H, OCH 3 ), 3.65 (m, 1H , H 7A ), 3.55 (dd, 1H, H 6A , 2.4 Hz), 3.50-3.40 (m, 3H, H 8 , D 1 ), 3.12 (dt, 1H, D 4 , J D 4-D 3 ax= J D - D 5 = 7.6 HZ, J D 4-D3eq= 4.4 Hz), 3.07 (dt, 1H, D 5 , J D5 -D6ax= 7.6 HZ, J D5 -D6eq= 4.4 HZ), 2.17-2.08 (m, 1H, D 3ax ), 2.10-2.02 (m, 1H, D 6ax ), 2.16 (s, 3H, C H 3 CO), 2.06 (s,
Page 1 and 2: (12) INTERNATIONAL APPLICATION PUBL
Page 3 and 4: mannose disaccharide (Manα1-2Man),
Page 5 and 6: It is a forth object of the inventi
Page 7 and 8: M' is a saccharidic or pseudo-sacch
Page 9 and 10: wherein Q and n are above disclosed
Page 12 and 13: wherein R is as above disclosed,
Page 14 and 15: may be made of gold, silver, Fe 2 O
Page 16 and 17: Within the compound of formula (I)
Page 18 and 19: wherein R and R 2 are as above repo
Page 20 and 21: through the Y linker and n is 1 to
Page 22 and 23: and (12a) 12b. As per a third aspec
Page 24 and 25: H wherein Q is selected from — N
Page 26 and 27: According to a second object of the
Page 28 and 29: wherein aj is 32 and J is a third g
Page 30 and 31: eactions requiring anhydrous condit
Page 34 and 35: 3H, CH 3 CO), 1.99 (s, 3H, CH 3 CO)
Page 36 and 37: To a solution of the compound 9 (12
Page 38 and 39: (C2 D ), 70.36 (C6 M ), 70.01 (C6 M
Page 40 and 41: EXAMPLE 2 Synthesis of compound 12a
Page 42 and 43: 13 C-NMR (100 MHz, D2 O) δ (ppm):
Page 44 and 45: (the R5 tropic laboratory-adapted s
Page 46 and 47: derived from 1 (see above); G3Man32
Page 48 and 49: CLAIMS: 1 A compound of general for
Page 50: OCH 3 ), hydroxymethyl (-CH 2 OH),
Page 53 and 54: alkyl chain, C1-C8 linear or branch
Page 55 and 56: 7 . A compound having the general f
Page 57 and 58: H wherein Q is selected from — N
Page 59: or methyl substituted 1,3-thiazole;
Page 62 and 63: wherein R 2 may be hydroxyl (-0H),
Page 64 and 65: 12. A compound according to claim 1
Page 66: or methyl substituted 1,3-thiazole;
Page 82 and 83:
INTERNATIONAL SEARCH REPORT C(Conti
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W0 2011/000721 A1 I||||||||||||||||||||||||||||||||||||||||||||||||||||||||| - Questel

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